Schematic diagram of complexes I through IV of the electron transport chain and ATP synthase. The red line traces the path of electrons as they enter and move along the electron transport chain. Complex I is shown at the far left as an L-shaped structure with one portion extending down into the mitochondrial matrix and the other portion embedded in the inner mitochondrial membrane. Ogilvie and colleagues used bioinformatics to perform a virtual whole genome subtraction of yeasts with or without complex I to find candidate complex I assembly factors, identified the human orthologs of these proteins, and showed that one of these orthologs, B17.2L, carried a null mutation in a patient with complex I deficiency (17). The authors also demonstrate that B17.2L — the first identified mammalian protein required for the normal assembly of human complex I — associates with an immature subcomplex of complex I (shown schematically) and facilitates complex I assembly. FADH₂, reduced flavin-adenine dinucleotide; CoQ, coenzyme Q (also known as ubiquinone).